Cancer Risk Rises as The Thymus Shrinks

We wanted to bring your attention to an open-access publication in which the researchers suggest that the age-related decline of the thymus is more important than DNA mutation as a cancer risk factor[1].

Repairing the damage

As we have discussed in this article, cancer is caused by DNA damage that creates mutations. Damage to our DNA happens all the time, and we have various repair systems in place for it.

While these systems are efficient, sooner or later, errors happen, and mutations slip through the net nonetheless. Cancer is essentially a game of chance; the more cells and cellular activity there are, the higher the chance a cancerous mutation will appear in one of those cells.

Environmental insults can also influence the chance of DNA damage and thus a potential mutation. Sunlight, harmful molecules in our bodies, radiation, and cellular stress can all influence the risk of damage and possible mutations.

We have cancer safety nets, but these fail as we age

Thankfully, even if a cancerous mutation does happen, we have a variety of systems that work to defend us by destroying these cells. Cells have internal safety systems such as those based on P53, which, upon detecting a cancerous mutation, cause the cell to destroy itself via programmed cell death, which is known as apoptosis.

The immune system is another way we defend ourselves from cancer, and we have a range of immune cells that are designed to seek out and destroy damaged, infected, and cancerous cells. Some of the most important immune cells in this battle against cancer are T cells. These cells are primarily created in the thymus, an immune organ that is located under the breastbone and produces the bulk of the T cells that patrol our bodies.

Unfortunately, as we age, our immune systems become increasingly ineffective and our thymi shrink, changing from T cell-producing tissue to fat. Some researchers believe that this happens due to signals that encourage new tissue to increasingly favor becoming adipose fat tissue over immune cell-producing tissue, and we talk about this in depth here. The end result is that our thymi ultimately lose the ability to produce new T cells, and we become vulnerable to infections, diseases, and cancer.

For this reason, there is a lot of interest in the research community in finding ways to rejuvenate the thymus so that it continues to produce T cells even in an older person. We have interviewed one researcher, Dr. Greg Fahy, about his work on thymic rejuvenation; should you wish to learn more, you can read about that here.

Conclusion

The rejuvenation of the thymus is of huge importance for combating diseases and keeping older people healthy. If the researchers in this paper are correct, and the immune system is more important than DNA mutation when it comes to cancer risk, then the need to rejuvenate the thymus is even more pressing.

The immune system performs a myriad of tasks, from combating invading pathogens and facilitating repair to clearing cellular debris, so it would be no surprise for this to be the case; the sooner we can restore the thymus to working order in older people, the better.

As a scientific writer and a devoted advocate of healthy longevity and the technologies to promote them, Steve has provided the community with hundreds of educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics.
His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).

“Although T-cells still enter the lymph system in older people, the scant T-cells that are produced can’t readily enter the lymph nodes. “The reason for that is the lymph nodes are undergoing profound changes with aging,” Nikolich-Zugich says.

In fact, researchers see a lot of fibrosis in the lymph node, meaning the connective bundles are starting to get thicker, less organized and less flexible.

“Lymph nodes aren’t able to effectively call in the cells from the outside, so fewer cells arrive,” he says. “Moreover, when the cells arrive, they don’t move inside like they should. Inside the lymph node is a superhighway meshwork, and we have found that this really gets messed up in aging.”

Scientists have tried rejuvenating only the thymus by blocking the body’s androgen production to increase its T-cell production, but increased, long-lasting immunity has proved elusive for the very reason that T-cells can’t gain entrance to the lymph nodes.

So, Nikolich-Zugich and his collaborators are formulating a novel plan of attack.

“There is one important part of this grant that is different from the approaches that people have been taking from the past,” Nikolich-Zugich says. “The novel idea here is that we want to rejuvenate both the thymus and the peripheral lymph organs, so both the factory that makes the cells and sites where the T-cells go to do the real work of defense against infection can once again work together.

“We feel like we will never get to rejuvenation if we work only on the thymus.”

In fact, the grant, sponsored by the National Institutes of Health, is a program project grant, which by design includes several interrelated individual projects, each run by Nikolich-Zugich and his collaborators. Some of the projects look at the thymus, others at the lymph nodes.”